Double-blind comparison of absorbable colloidal bismuth subcitrate and nonabsorbable bismuth subnitrate in the eradication of Helicobacter pylori and the relief of nonulcer dyspepsia

Background. Bismuth is widely used for the eradication of H. pylori , especially in developing countries, although there are concerns over its neurotoxicity. Whether bismuth has to be absorbed in humans to act against H. pylori is not known. In this study, we compared "absorbable" (colloidal bismuth subcitrate) and "nonabsorbable" (bismuth subnitrate) bismuth as part of triple therapy in the eradication of H. pylori.
Materials and Methods. A double-blind, randomized, placebo-controlled trial was carried out with 120 H. pylori –positive patients with nonulcer dyspepsia. Group CBS + Ab (n = 35) received colloidal bismuth subcitrate (one tablet qds), amoxicillin (500 mg qds), and metronidazole (400 mg tds). Group BSN + Ab (n = 35) received bismuth subnitrate (two tablets tds) and the same antibiotics. Group Ab (n = 35) received placebo bismuth (two tablets tds) and the antibiotics. Group BSN (n = 15) received bismuth subnitrate (two tablets tds) and placebo antibiotics. Bismuth was taken for 4 weeks and the antibiotics for the first 2 weeks. H. pylori eradication, side effects, compliance, pre- and post-treatment symptom scores, and bismuth absorption were assessed.
Results. H. pylori eradication was 69%, 83%, 31%, and 0% in CBS + Ab, BSN + Ab, Ab, and BSN, respectively. Side effects, compliance, and symptom relief were similar in all groups, but blood bismuth levels were significantly greater in CBS + Ab than the other three groups.
Conclusion. The efficacy of bismuth-based therapies as part of triple therapy in the eradication of H. pylori is unrelated to absorption. Hence, the use of effective but poorly absorbed bismuth preparations should be encouraged for bismuth-based eradication therapies.     

雷贝拉唑、阿莫西林联合胶体果胶铋治疗Hp阳性消化性溃疡的临床研究

目的 探讨雷贝拉唑、阿莫西林联合胶体果胶铋治疗幽门螺杆菌（Helicobacter pylori,Hp）阳性消化性溃疡的临床疗效。方法 选取116例Hp阳性消化性溃疡患者,将其随机分为对照组和观察组,对照组给予雷贝拉唑、阿莫西林进行治疗,观察组给予雷贝拉唑、阿莫西林联合胶体果胶铋进行治疗。两组均连续治疗4周。观察两组患者的主要症状变化情况、临床疗效、Hp清除率及不良反应等。结果 经治疗后,观察组临床总有效率为94.8%,与对照组总有效率74.1%比较,差异有统计学意义（χ2=4.735,P＜0.05）;观察组上腹疼痛、反酸、腹胀等症状改善所需时间与对照组比较,差异均有统计学意义（t分别为7.557、4.067、9.346,Ps＜0.05）;观察组Hp清除率91.4%与对照组Hp清除率65.5%比较,差异有统计学意义（χ2=5.736,P＜0.05）;观察组不良反应发生率19.0%与对照组不良反应发生率20.7%比较,差异无统计学意义（χ2=0.027,P>0.05）。结论 雷贝拉唑、阿莫西林联合胶体果胶铋用于治疗Hp阳性消化性溃疡,可显著改善临床症状,提高Hp清除率和临床疗效,且安全性较好,具有一定的临床意义。     

Interaction between prostacyclin and colchicine on the gastric mucosa of rat in different experimental ulcer models

The effect of prostacyclin and colchicine on the fundic gastric mucosa of adult female Wistar rats was investigated in stress (immobilization) and indomethacin induced ulcer models. Under prostacyclin treatment the ulcer index decreased significantly in both ulcer models. This effect was inhibited by colchicine. The nuclear volume of fundic epithelial cells increased significantly after application of either type of ulcerogenic stimulus. Prostacyclin did not influence the nuclear volume changes in stress ulcer, while it prevented this phenomenon in indomethacin-induced ulceration. Following colchicine treatment the nuclear volume decreased in both ulcer models. After combined prostacyclin and colchicine treatment the nuclear shrinkage remained unaltered in stress ulcer, while in indomethacin ulcer the nuclear volume decreasing effect of the separately administered drugs disappeared after combined treatment. The latter phenomenon was interpreted as an antagonistic interaction between prostacyclin and colchicine.     

Substrate specificity of lysophospholipase-transacylase from rat lung and its action on various physical forms of lysophosphatidylcholine

Lysophospholipase-transacylase (lysolecithin acylhydrolase, EC 3.1.1.5) from rat lung catalyzes the transfer of acyl groups from lysophosphatidylcholine to either water or another molecule of lysophosphatidylcholine. Studies on the substrate specificity of the purified enzyme showed that a phosphate group in the substrate is essential for enzymatic activity; monoacylglycerol is not hydrolyzed, nor does it serve as an acceptor of acyl groups. The influence of the acyl chain in lysophosphatidylcholine was investigated by using mixtures of differently labelled lysophosphatidylcholine species, or by studying the transfer of [1-¹⁴C]Palmitate from [1-¹⁴C]palmitoylpropane (1,3)diol-phosphocholine to various 1-acyl-sn-glycero-3-phosphocholines. Lysophosphatidylcholines with acyl chains comprised of ten or more C-atoms were found to serve as acyl acceptors. This finding was used to determine the action of the enzyme on 1-[1-¹⁴C]lauroyl- and 1[1-¹⁴C]myristoyl-sn-glycero-3-phosphocholine both below and above the critical micelle concentration of the substrate. Monomeric substrate was effectively hydrolyzed, but the transacylase activity of the enzyme was only expressed when substrate micelles were present. Likewise, no transacylase activity was found when lysophosphatidylcholine was embedded in liposomal membranes prepared from lung total lipids. These findings, which persist with crude enzyme preparations (100 000 × g supernatant), are discussed in relation to the putative function of the lysophospholipase-transacylase in the synthesis of disaturated phosphatidylcholine in lung.     

Inhibition of urease by bismuth(III): Implications for the mechanism of action of bismuth drugs

Bismuth compounds are widely used for the treatment of peptic ulcers and Helicobacter pylori infections. It has been suggested that enzyme inhibition plays an important role in the antibacterial activity of bismuth towards this bacterium. Urease, an enzyme that converts urea into ammonia and carbonic acid, is crucial for colonization of the acidic environment of the stomach by H. pylori. Here, we show that three bismuth complexes exhibit distinct mechanisms of urease inhibition, with some differences dependent on the source of the enzyme. Bi(EDTA) and Bi(Cys)₃ are competitive inhibitors of jack bean urease with K _i values of 1.74 ± 0.14 and 1.84 ± 0.15 mM, while the anti-ulcer drug, ranitidine bismuth citrate (RBC) is a non-competitive inhibitor with a K _i value of 1.17 ± 0.09 mM. A ¹³C NMR study showed that Bi(Cys)₃ reacts with jack bean urease during a 30 min incubation, releasing free cysteines from the metal complex. Upon incubation with Bi(EDTA) and RBC, the number of accessible cysteine residues in the homohexameric plant enzyme decreased by 5.80 ± 0.17 and 11.94 ± 0.13, respectively, after 3 h of reaction with dithiobis(2-nitrobenzoic acid). Kinetic analysis showed that Bi(EDTA) is both a competitive inhibitor and a time-dependent inactivator of the recombinant Klebsiella aerogenes urease. The active C319A mutant of the bacterial enzyme displays a significantly reduced sensitivity toward inactivation by Bi(EDTA) compared with the wild-type enzyme, consistent with binding of Bi³⁺ to the active site cysteine (Cys³¹⁹) as the mechanism of enzyme inactivation.     

Regeneration of the rat sciatic nerve after various experimental lesions (morphologic and morphometric analysis)

Dynamics of structural restoration of the peripheral nerve (n. ischiadicus) have been studied in the noninbred rats in 3 series of experiments: after local freezing, pinching and cutting with a subsequent connection of the nerve ends by means of an implanted arterial vessel. As demonstrate the methods of light and electron microscopy, myelinization of the nervous fibers in the distal part of the nerve begins between the 10th-20th days after the effect. Further, amount of the myelinated nerve fibers (NF) significantly increases, they become essentially thicker. However, even in the later time of the observation (9 months) most of NF remain thinner than in the control nerve; this demonstrates that the reparative processes take a longer time than it was supposed before. The comparative analysis makes it possible to recommend the cryogenic lesion of the nerve as the most perspective model to study processes of the reparative histogenesis. Certain positive signs of sutureless connection of the cut nerve by means of the implanted arterial vessel are noted for clinical substitution of vast diastases of the nerve.     

左金丸对实验性应激性胃溃疡的保护作用及其机制

目的探讨中药左金丸对因束缚-水浸应激引起的大鼠应激性胃溃疡胃黏膜损伤的保护作用的影响,并初步探讨其作用机制。方法将60只健康SD雄性大鼠随机分为6组,即空白对照组、模型对照组、阳性对照组、左金丸低剂量组、左金丸中剂量组和左金丸高剂量组。连续灌胃给药5 d,末次给药后禁食不禁水24 h,采用"束缚-水浸"应激法制备大鼠应激性胃溃疡模型。造模成功后进行胃体形态学观察,测量胃液p H值,计算胃溃疡指数(UI),并用酶联免疫法检测血清中前列腺素E2(PGE2)的含量。结果(1)与空白对照组比较,模型对照组大鼠胃液p H值明显降低、胃黏膜损伤指数(UI)显著升高(P0.01);与模型对照组比较,阳性对照组、左金丸中、高剂量组大鼠胃液p H值明显升高,UI明显下降(P0.01);与阳性对照组比较,左金丸高剂量组大鼠胃液p H值和UI差异无统计学意义(P0.05)。(2)与空白对照组比较,模型对照组大鼠血清中PGE2含量显著降低(P0.01);与模型对照组比较,阳性对照组和左金丸高、中剂量组大鼠血清中PGE2含量均显著升高(P0.01);与阳性对照组比较,左金丸中、高剂量组大鼠血清中PGE2的含量差异无统计学意义(P0.05)。结论 (1)左金丸对应激性胃溃疡大鼠胃黏膜具有保护作用。(2)左金丸通过升高大鼠胃液p H值和提高血清中PGE2含量,达到降低胃黏膜攻击因素和增强胃黏膜防御功能的作用,从而起到保护大鼠胃黏膜的作用。左金丸可以预防应激性胃溃疡的发生并能促进胃溃疡的愈合,其作用机制可能与提高胃液p H值从而降低胃黏膜攻击因素,促进PGE2释放从而增强胃黏膜防御功能等因素有关。(3)左金丸对应激性胃溃疡胃黏膜的保护作用在一定范围内与其浓度呈正相关关系。     

Kinetics and collagenolytic role of eosinophils in chronic gastric ulcer in the rat

 An association between eosinophils and tissue damage has been observed in numerous disorders. However, few reports have addressed the role of infiltrating eosinophils in gastric ulcer healing. The aim of this study was to investigate the kinetics and role of eosinophils infiltrating experimental chronic gastric ulcers in the rat. We developed a monoclonal antibody against human matrix metalloproteinase 1 (MMP1) purified from conditioned culture medium of human skin fibroblasts. Acetic acid-induced gastric ulcers were resected from rats on days 1, 3, 5, 10, 20, 40, and 180 after the days of induction (day 0). Tissue specimens were immunostained with this antibody and examined with an electron microscope. Few eosinophils were observed in the granulation tissue until day 20. By days 40 and 180, MMP1-positive eosinophils had increased in the granulation tissue of open ulcers. Azan staining revealed dispersed collagen fibers around infiltrating eosinophils. In contrast, scars demonstrated few eosinophils in fibrous tissue on days 40 and 180. Eosinophils which express MMP1 infiltrate granulation tissue at the chronic stage of gastric ulceration. The results suggest that eosinophils may play a role in tissue remodeling and deterioration of ulceration. Accepted: 18 March 1997     

Effect of cytoprotective and antiulcer drugs on the healing process of subacute gastric ulcer in rat (a new model)

It has been developed by us a simple new method for producing subacute gastric ulcer in rats, combined with a novel method for the quantitative evaluation of the healing process. Fasted rats with 120-150 g were used. The animals were anaesthesized by ether and than a polyethylene chateter was orally inserted into the stomach with a fine needle inside. After the cannule reached the gastric wall, the needle was pressed gently so as to punch the gastric wall. Drugs under study were administered orally 30 min and 24 h after the puncture. Food and water were given ad libitum from 2 h after the intervention until the end (96 h) of experiments. In order to follow the healing process of subacute ulcer, the so-called tensile strength of the ulcer was determined by inflating and expressed in mmHg. The healing rate was calculated. The antiulcer drugs: Cimetidine, Famotidin, Pirenzepine and sucralfate dose dependently and significantly increased the healing rate of ulcer. Non steroidal antiinflammatory drugs: naproxen, piroxicam, indomethacin and ibuprofen significantly delayed the healing of ulcer. ASA showed tendency to delay the healing. Strong HCl (0.5 molar) significantly delayed the healing of ulcer. N-EM given subcutaneously dose dependently delayed the healing of subacute ulcer.